tbuckley/cabot-search huggingface dataset:
Factors Associated With COVID-19 Vaccination Among Individuals With Vaccine Hesitancy in French-Speaking Belgium
Authors: Gloria Yawavi Gbenonsi, Aline Labat, Amandine Oleffe, Boris Jidovtseff, Olivier Servais, Nicolas Vermeulen, Elisabeth Paul
Journal: JAMA Network Open (2022)

This cross-sectional study examines why people in French-speaking regions of Belgium who initially resisted getting the COVID-19 vaccine eventually chose to get vaccinated.
Prostate Cancer Transcriptomic Regulation by the Interplay of Germline Risk Alleles, Somatic Mutations, and 3D Genomic Architecture
Authors: Jiapei Yuan, Kathleen E. Houlahan, Susmita G. Ramanand, Sora Lee, GuemHee Baek, Yang Yang, Yong Chen, Douglas W. Strand, Michael Q. Zhang, Paul C. Boutros, Ram S. Mani
Journal: Cancer Discovery (2022)

Prostate cancer is one of the most heritable human cancers. Genome-wide association studies have identified at least 185 prostate cancer germline risk alleles, most noncoding. We used integrative three-dimensional (3D) spatial genomics to identify the chromatin interaction targets of 45 prostate cancer risk alleles, 31 of which were associated with the transcriptional regulation of target genes in 565 localized prostate tumors. To supplement these 31, we verified transcriptional targets for 56 additional risk alleles using linear proximity and linkage disequilibrium analysis in localized prostate tumors. Some individual risk alleles influenced multiple target genes; others specifically influenced only distal genes while leaving proximal ones unaffected. Several risk alleles exhibited widespread germline-somatic interactions in transcriptional regulation, having different effects in tumors with loss of PTEN or RB1 relative to those without. These data clarify functional prostate cancer risk alleles in large linkage blocks and outline a strategy to model multidimensional transcriptional regulation. Many prostate cancer germline risk alleles are enriched in the noncoding regions of the genome and are hypothesized to regulate transcription. We present a 3D genomics framework to unravel risk SNP function and describe the widespread germline-somatic interplay in transcription control. This article is highlighted in the In This Issue feature, p. 2711.
Association of Social Risk Factors With Mortality Among US Adults With a New Cancer Diagnosis
Authors: Matthew P. Banegas, John F. Dickerson, Zhiyuan Zheng, Caitlin C. Murphy, Reginald Tucker-Seeley, James D. Murphy, K. Robin Yabroff
Journal: JAMA Network Open (2022)

This cohort study examines the associations of multiple social risk factors with mortality risk among patients newly diagnosed with cancer in the US.
Prevalence and Risk Factors for Medical Debt and Subsequent Changes in Social Determinants of Health in the US
Authors: David U. Himmelstein, Samuel L. Dickman, Danny McCormick, David H. Bor, Adam Gaffney, Steffie Woolhandler
Journal: JAMA Network Open (2022)

Cost barriers discourage many US residents from seeking medical care and many who obtain it experience financial hardship. However, little is known about the association between medical debt and social determinants of health (SDOH).To determine the prevalence of and risk factors associated with medical debt and the association of medical debt with subsequent changes in the key SDOH of food and housing security.Cross-sectional analyses using multivariable logistic regression models controlled for demographic, financial, insurance, and health-related factors, and prospective cohort analyses assessing changes over time using the 2018, 2019, and 2020 Surveys of Income and Program Participation. Participants were nationally representative samples of US adults surveyed for 1 to 3 years.Insurance-related and health-related characteristics as risk factors for medical debt; Newly incurred medical debt as a risk factor for deterioration in SDOHs.Prevalence and amounts of medical debt; 4 SDOHs: inability to pay rent or mortgage or utilities; eviction or foreclosure; and food insecurity.Among 51 872 adults surveyed regarding 2017, 40 784 regarding 2018 and 43 220 regarding 2019, 51.6% were female, 16.8% Hispanic, 6.0% were non-Hispanic Asian, 11.9% non-Hispanic Black, 62.6% non-Hispanic White, and 2.18% other non-Hispanic. A total of 10.8% (95% CI, 10.6-11.0) of individuals and approximately 18.1% of households carried medical debt. Persons with low and middle incomes had similar rates: 15.3%; (95% CI,14.4-16.2) of uninsured persons had debt, as did 10.5% (95% CI, 10.2-18.8) of the privately-insured. In 2018 the mean medical debt was $21 687/debtor (median $2000 [IQR, $597-$5000]). In cross-sectional analyses, hospitalization, disability, and having private high-deductible, Medicare Advantage, or no coverage were risk factors associated with medical indebtedness; residing in a Medicaid-expansion state was protective (2019 odds ratio [OR], 0.76; 95% CI, 0.70-0.83). Prospective findings were similar, eg, losing insurance coverage between 2017 and 2019 was associated with acquiring medical debt by 2019 (OR, 1.63; 95% CI, 1.23-2.14), as was becoming newly disabled (OR, 2.42; 95% CI, 1.95-3.00) or newly hospitalized (OR, 2.95; 95% CI, 2.40-3.62). Acquiring medical debt between 2017 and 2019 was a risk factor associated with worsening SDOHs, with ORs of 2.20 (95% CI,1.58-3.05) for becoming food insecure; 2.29 (95% CI, 1.73-3.03) for losing ability to pay rent or mortgage; 2.37 (95% CI, 1.75-3.23) for losing ability to pay utilities; and 2.95 (95% CI, 1.38-6.31) for eviction or foreclosure in 2019.In this cross-sectional and cohort study, medical indebtedness was common, even among insured individuals. Acquiring such debt may worsen SDOHs. Expanded and improved health coverage could ameliorate financial distress, and improve housing and food security.
Changes in Emergency Department Visits for Cannabis Hyperemesis Syndrome Following Recreational Cannabis Legalization and Subsequent Commercialization in Ontario, Canada
Authors: Daniel Thomas Myran, Rhiannon Roberts, Michael Pugliese, Monica Taljaard, Peter Tanuseputro, Rosalie Liccardo Pacula
Journal: JAMA Network Open (2022)

Importance Prior research suggests that the legalization of recreational cannabis is associated with increases in cannabis hyperemesis syndrome (CHS), but it is unclear how cannabis commercialization (ie, greater retail store access as well as increased variety and potency of cannabis products) may be associated with these changes. Objectives To examine changes in the number and characteristics of CHS emergency department (ED) visits from before to after legalization of cannabis in Ontario, Canada. Design, Setting, and Participants This repeated cross-sectional study used interrupted time-series analyses to examine immediate and gradual changes in ED visits for CHS in Ontario, Canada, during 3 time periods: prelegalization (January 2014-September 2018), legalization with product and retail store restrictions (October 2018-February 2020), and commercialization with new products and expanded stores, which coincided with the COVID-19 pandemic (March 2020-June 2021). Data were obtained from routinely collected and linked health administrative databases. All individuals aged at least 15 years and who were eligible for Ontario’s Universal Health Coverage were included. Data were analyzed between March and July 2022. Main Outcomes and Measures Monthly counts of ED visits for CHS per capita. Results There were 12 866 ED visits for CHS from 8140 individuals during the study. Overall, the mean (SD) age was 27.4 (10.5) years, with 2834 individuals (34.8%) aged 19 to 24 years, 4163 (51.5%) females, and 1353 individuals (16.6%) with a mental health ED visit or hospitalization in the 2 years before their first CHS ED visit. Nearly 10% of visits (1135 visits [8.8%]) led to hospital admissions. Monthly rates of CHS ED visits increased 13-fold during the 7.5-year study period, from 0.26 visits per 100 000 population in January 2014 to 3.43 visits per 100 000 population in June 2021. Legalization was not associated with an immediate or gradual change in rates of ED visits for CHS; however, commercialization during the COVID-19 pandemic period was associated with an immediate increase in rates of CHS ED visits (incidence rate ratio [IRR], 1.49; 95% CI, 1.31-1.70). During commercialization, rates of CHS ED visits increased more in women (IRR, 1.49; 95% CI, 1.16-1.92) and individuals older than the legal age of cannabis purchase (eg, age 19-24 years: IRR, 1.60; 95% CI, 1.19-2.16) than men (IRR, 1.08; 95% CI, 0.85-1.37) and individuals younger than the legal age of purchase (IRR, 0.78; 95% CI, 0.42-1.45). Conclusions and Relevance This cross-sectional study found large increases in CHS ED visits during the period of time when the market commercialized and the COVID-19 pandemic occurred. Greater awareness of CHS symptoms by ED staff in regions where legal commercialized cannabis markets exist is indicated.
Comparison of 1-Year Health Care Expenditures and Utilization Following Minimally Invasive vs Open Nephrectomy
Authors: Kennedy E. Okhawere, Gediwon Milky, I-Fan Shih, Yanli Li, Ketan K. Badani
Journal: JAMA Network Open (2022)

Importance Given the widespread adoption and clinical benefits of minimally invasive surgery approaches (MIS) in partial nephrectomy (PN) and radical nephrectomy (RN), assessment of long-term cost implications is relevant. Objective To compare health care utilization and expenditures within 1 year after MIS and open surgery (OS). Design, Setting, and Participants This cohort study was conducted using a US commercial claims database between 2013 and 2018. A total of 5104 patients aged 18 to 64 years who underwent PN or RN for kidney cancer and were continuously insured for 180 days before and 365 days after surgery were identified. An inverse probability of treatment weighting analysis was performed to examine differences in costs and use of health care services. Exposures Surgical approach (MIS or OS). Main Outcomes and Measures Outcomes assessed included 1-year total health care expenditure, health care utilizations, and estimated days missed from work. Results Of the 5104 patients, 2639 had PN (2008 MIS vs 631 OS) and 2465 had RN (1816 MIS vs 649 OS) and most were male (PN: 1657 [62.8%]; RN: 399 [63.1%]) and between 55 and 64 years of age (PN: 1034 [51.3%]; RN: 320 [55.7%]). Patients who underwent MIS had lower index hospital length of stay compared with OS (mean [95% CI] for PN: 2.45 [2.37-2.53] vs 3.78 [3.60-3.97] days; P &amp;lt; .001; for RN: 2.82 [2.73-2.91] vs 4.62 [4.41-4.83] days; P &amp;lt; .001), and lower index expenditure for RN ($28 999 [$28 243-$29 796] vs $31 977 [$30 729-$33 329]; P &amp;lt; .001). For PN, index expenditure was lower for OS than MIS (mean [95% CI], $27 480 [$26 263-$28 753] vs $30 380 [$29614-$31 167]; P &amp;lt; .001). Patients with MIS had lower 1-year postdischarge readmission rate (PN: 15.1% vs 21.5%; odds ratio [OR], 0.65; 95% CI, 0.52-0.82; P &amp;lt; .001; RN: 15.6% vs 18.9%; OR, 0.79; 95% CI, 0.63-1.00; P = .05), and fewer hospital outpatient visits (mean [95% CI] for PN: 4.69 [4.48-4.90] vs 5.25 [4.84-5.66]; P = .01; RN: 5.50 [5.21-5.80] vs 6.71 [6.12-7.30]; P &amp;lt; .001) than those with OS. For RN, MIS was associated with 1.47 fewer missed workdays (95% CI, 0.57-2.38 days; P = .001). The reduction in health care use in MIS was associated with lower or similar total cumulative expenditures compared with OS (mean difference [95% CI] for PN: $331 [–$3250 to $3912]; P = .85; for RN: –$11 265 [–$17 065 to –$5465]; P &amp;lt; .001). Conclusions and Relevance In this cohort study, MIS was associated with lower or similar total cumulative expenditure than OS in the period 1 year after discharge from the index surgery. These findings suggest that downstream expenditures and resource utilization should be considered when evaluating surgical approach for nephrectomy.
Assessment of the Clinical Utility of Pretreatment<i>DPYD</i>Testing for Patients Receiving Fluoropyrimidine Chemotherapy
Authors: Daniel L. Hertz
Journal: Journal of Clinical Oncology (2022)

Patients who carry pathogenic variants in DPYD have higher systemic fluoropyrimidine (FP) concentrations and greater risk of severe and fatal FP toxicity. Pretreatment DPYD testing and DPYD-guided FP dosing to reduce toxicity and health care costs is recommended by European clinical oncology guidelines and has been adopted across Europe, but has not been recommended or adopted in the United States. The cochairs of the National Comprehensive Cancer Network Guidelines for colon cancer treatment explained their concerns with recommending pretreatment DPYD testing, particularly the risk that reduced FP doses in DPYD carriers may reduce treatment efficacy.This special article uses previously published frameworks for assessing the clinical utility of cancer biomarker tests, including for germline indicators of toxicity risk, to assess the clinical utility of pretreatment DPYD testing, with a particular focus on the risk of reducing treatment efficacy.There is no direct evidence of efficacy reduction, and the available indirect evidence demonstrates that DPYD-guided FP dosing results in similar systemic FP exposure and toxicity compared with standard dosing in noncarriers, and is well calibrated to the maximum tolerated dose, strongly suggesting there is minimal risk of efficacy reduction.This article should serve as a call to action for clinicians and clinical guidelines committees in the United States to re-evaluate the clinical utility of pretreatment DPYD testing. If clinical utility has not been demonstrated, further dialogue is needed to clarify what additional evidence is needed and which of the available study designs, also described within this article, would be appropriate. Clinical guideline recommendations for pretreatment DPYD testing would increase clinical adoption and ensure that all patients receive maximally safe and effective FP treatment.
HNRNPA2B1: RNA-Binding Protein That Orchestrates Smooth Muscle Cell Phenotype in Pulmonary Arterial Hypertension
Authors: Grégoire Ruffenach, Lejla Medzikovic, Laila Aryan, Min Li, Mansoureh Eghbali
Journal: Circulation (2022)

RNA-binding proteins are master orchestrators of gene expression regulation. They regulate hundreds of transcripts at once by recognizing specific motifs. Thus, characterizing RNA-binding proteins targets is critical to harvest their full therapeutic potential. However, such investigation has often been restricted to a few RNA-binding protein targets, limiting our understanding of their function. In cancer, the RNA-binding protein HNRNPA2B1 (heterogeneous nuclear ribonucleoprotein A2B1; A2B1) promotes the pro-proliferative/anti-apoptotic phenotype. The same phenotype in pulmonary arterial smooth muscle cells (PASMCs) is responsible for the development of pulmonary arterial hypertension (PAH). However, A2B1 function has never been investigated in PAH.Through the integration of computational and experimental biology, the authors investigated the role of A2B1 in human PAH-PASMC. Bioinformatics and RNA sequencing allowed them to investigate the transcriptome-wide function of A2B1, and RNA immunoprecipitation and A2B1 silencing experiments allowed them to decipher the intricate molecular mechanism at play. In addition, they performed a preclinical trial in the monocrotaline-induced pulmonary hypertension rat model to investigate the relevance of A2B1 inhibition in mitigating pulmonary hypertension severity.They found that A2B1 expression and its nuclear localization are increased in human PAH-PASMC. Using bioinformatics, they identified 3 known motifs of A2B1 and all mRNAs carrying them. In PAH-PASMC, they demonstrated the complementary nonredundant function of A2B1 motifs because all motifs are implicated in different aspects of the cell cycle. In addition, they showed that in PAH-PASMC, A2B1 promotes the expression of its targets. A2B1 silencing in PAH-PASMC led to a decrease of all tested mRNAs carrying an A2B1 motif and a concomitant decrease in proliferation and resistance to apoptosis. Last, in vivo A2B1 inhibition in the lungs rescued pulmonary hypertension in rats.Through the integration of computational and experimental biology, the study revealed the role of A2B1 as a master orchestrator of the PAH-PASMC phenotype and its relevance as a therapeutic target in PAH.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2022)

Breaking Insights| September 16 2022 Highlights from Recent Cancer Literature Author & Article Information Online ISSN: 1538-7445 Print ISSN: 0008-5472 ©2022 American Association for Cancer Research2022American Association for Cancer Research Cancer Res (2022) 82 (18): 3189–3190. https://doi.org/10.1158/0008-5472.CAN-82-18-BI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record September 16 2022 Citation Highlights from Recent Cancer Literature. Cancer Res 15 September 2022; 82 (18): 3189–3190. https://doi.org/10.1158/0008-5472.CAN-82-18-BI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Although BRCA1/2 alterations have been reported to predict platinum sensitivity, BRCA1 alterations have not consistently correlated with platinum sensitivity in clinical trials. Menghi and colleagues have now identified an explanation for these discordant results. They found that in contrast to BRCA1/2 mutations, BRCA1 promoter methylation (BRCA1meth) was not correlated with response to platinum agents in triple-negative breast and ovarian cancer patients. In vivo studies revealed that BRCA1meth is lost during chemotherapy treatment, leading to BRCA1 reactivation and acquired platinum resistance. Expert Commentary: This study suggests that the reversibility of BRCA1meth may explain the inconsistent platinum efficacy observed in BRCA1-deficient tumors. Menghi F, Banda K, Kumar P, Straub R, Dobrolecki L, Rodriguez IV, et al. Genomic and epigenomic BRCA alterations predict adaptive resistance and response to platinum-based therapy in patients with triple-negative breast and ovarian carcinomas. Science Translational Medicine 2022;14:eabn1926. doi: 10.1126/scitranslmed.abn1926. Promoter methylation of the... You do not currently have access to this content.
Neutrophilic eccrine hidradenitis in a pediatric patient with acute myeloid leukemia
Authors: Rachelle Zipper, Valerie Fong, Michelle Toker, Nithin Reddy, Pooja Srivastava, Bijal Amin, Adit Tal, Benedict Wu, Brenda I. Anosike
Journal: American Journal of Hematology (2022)

All authors have no associations that might pose a conflict of interest. Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. Figure S1 Timeline of overall clinical presentation, treatment, and response to therapy during hospitalization. Table S1 Lab results obtained on admission = Hospital Day (HD)1; Lab results on Hospital Day 14 = initiation date of liposomal amphotericin B and date of skin punch biopsy. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
COVID-19 mRNA vaccine effectiveness (second and first booster dose) against hospitalisation and death during Omicron BA.5 circulation: cohort study based on electronic health records, Portugal, May to July 2022
Authors: Irina Kislaya, Ausenda Machado, Sarah Magalhães, Ana Paula Rodrigues, Rafael Franco, Pedro Pinto Leite, Carlos Matias Dias, Baltazar Nunes
Journal: Eurosurveillance (2022)

We measured vaccine effectiveness (VE) against COVID-19-related severe outcomes in elderly people in Portugal between May and July 2022. In ≥ 80 year-olds, the second booster dose VE was 81% (95% CI: 75–85) and 82% (95% CI: 77–85), respectively, against COVID-19-related hospitalisation and death. The first booster dose VE was 63% (95% CI: 55–70) in ≥ 80 year-olds and 74% (95% CI: 66–80) in 60–79 year-olds against hospitalisation, and 63% (95% CI: 57–69) and 65% (95% CI: 54–74) against death.
Genetic regulation of RNA splicing in human pancreatic islets
Authors: Goutham Atla, Silvia Bonàs-Guarch, Mirabai Cuenca-Ardura, Anthony Beucher, Daniel J. M. Crouch, Javier Garcia-Hurtado, Ignasi Moran, Miriam Cnop, Lena Eliasson, Jonathan Lou S. Esguerra, Décio L. Eizirik, Leif Groop, Thomas S. Jensen, Torben Hansen, Piero Marchetti, Josep M. Mercader, Hindrik Mulder, Chris R. Stabile-Barnett, Christian Thirion, David Torrents, Manuel Irimia, Rashmi B. Prasad, Anna L. Gloyn, Lorella Marselli, Mara Suleiman, Thierry Berney, Eelco J. P. de Koning, Julie Kerr-Conte, Francois Pattou, John A. Todd, Lorenzo Piemonti, Jorge Ferrer
Journal: Genome biology (2022)

Abstract Background Non-coding genetic variants that influence gene transcription in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D), and likely also contribute to type 1 diabetes (T1D) risk. For many loci, however, the mechanisms through which non-coding variants influence diabetes susceptibility are unknown. Results We examine splicing QTLs (sQTLs) in pancreatic islets from 399 human donors and observe that common genetic variation has a widespread influence on the splicing of genes with established roles in islet biology and diabetes. In parallel, we profile expression QTLs (eQTLs) and use transcriptome-wide association as well as genetic co-localization studies to assign islet sQTLs or eQTLs to T2D and T1D susceptibility signals, many of which lack candidate effector genes. This analysis reveals biologically plausible mechanisms, including the association of T2D with an sQTL that creates a nonsense isoform in ERO1B , a regulator of ER-stress and proinsulin biosynthesis. The expanded list of T2D risk effector genes reveals overrepresented pathways, including regulators of G-protein-mediated cAMP production. The analysis of sQTLs also reveals candidate effector genes for T1D susceptibility such as DCLRE1B , a senescence regulator, and lncRNA MEG3 . Conclusions These data expose widespread effects of common genetic variants on RNA splicing in pancreatic islets. The results support a role for splicing variation in diabetes susceptibility, and offer a new set of genetic targets with potential therapeutic benefit.